Publications

The synthesis of a series of N-aminoimidazoles (NAIMs) with an uncommon spectrum of antiretroviral activity is described. From a group of 60 closely related molecules, we were able to subdivide the molecules in different groups based on their anti-HIV and anti-SIV activity in vitro: (i) molecules acting on a new, immediate postintegration step, (ii) molecules acting on both postintegration and HIV-1 reverse transcriptase (RT) as NNRTI, and (iii) molecules that mainly act at the HIV-1 RT according to an NNRTI-type mode of action.

Bicyclic furano pyrimidine analogues have been shown to be potent and selective inhibitors of varicella-zoster virus (VZV). Our initial compounds bearing a C8-C10 side chain showed ca 300-fold incr...

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Dual-tropic human immunodeficiency virus type 1 (HIV-1) strains infect both primary macrophages and transformed T-cell lines. Prototype T-cell line-tropic (T-tropic) strains use CXCR4 as their principal entry coreceptor (X4 strains), while macrophagetropic (M-tropic) strains use CCR5 (R5 strains). Prototype dual tropic strains use both coreceptors (R5X4 strains). Recently, CXCR4 expressed on macrophages was found to support infection by certain HIV-1 isolates, including the dual-tropic R5X4 strain 89.6, but not by T-tropic X4 prototypes like 3B. To better understand the cellular basis for dual tropism, we analyzed the macrophage coreceptors used for Env-mediated cell-cell fusion as well as infection by several dual-tropic HIV-1 isolates. Like 89.6, the R5X4 strain DH12 fused with and infected both wild-type and CCR5-negative macrophages. The CXCR4-specific inhibitor AMD3100 blocked DH12 fusion and infection in macrophages that lacked CCR5 but not in wild-type macrophages. This finding indicates two independent entry pathways in macrophages for DH12, CCR5 and CXCR4. Three primary isolates that use CXCR4 but not CCR5 (tybe, UG021, and UG024) replicated efficiently in macrophages regardless of whether CCR5 was present, and AMD3100 blocking of CXCR4 prevented infection in both CCR5 negative and wild-type macrophages. Fusion mediated by UG021 and UG024 Envs in both wild-type and CCR5-deficient macrophages was also blocked by AMD3100. Therefore, these isolates use CXCR4 exclusively for entry into macrophages. These results confirm that macrophage CXCR4 can be used for fusion and infection by primary HIV-1 isolates and indicate that CXCR4 may be the sole macrophage coreceptor for some strains. Thus, dual tropism can result from two distinct mechanisms: utilization of both CCR5 and CXCR4 on macrophages and T-cell lines, respectively (dual-tropic R5X4), or the ability to efficiently utilize CXCR4 on both macrophages and T-cell lines (dual-tropic X4).

Both therapy strategies, switching ddC to 3TC or adding 3TC, significantly improved the virological and immunological efficacy compared with continuing ZDV/ddC. Our results support the use of 3TC in patients previously treated with the ZDV/ddC combination.

Coordinate measurement machine (CMM) probing techniques can involve direct mechanical contact (e.g., tactile probing) or diverse non-contact principles (e.g., laser line scan probing). For some applications, contact methods are not capable of measuring fast enough to ensure 100% quality controlled parts. A laser line scanning probe uses a laser triangulation-based method to acquire 3D measurement points on a workpiece relative to a sensor. Mounting the sensor in a 3D coordinate frame, e.g., in a CMM provides enough information to fully examine the workpiece. These techniques are most commonly exploited in medical industry and industries involving plate materials. A high data density and measurement speed are significant advantages when measuring free-form surfaces by laser line scanning, making the process much more time-efficient. However, high-precision geometrical features (such as cylinders, spheres, etc.) must be measured for locating and aligning the free-form shapes. The accuracy of the equipment therefore has to be assessed. Probe Maximum Permissible Error (MPE P ) values below 10μm have been reported for cutting-edge laser line scanners. This paper compares the major influences on measurements on cylindrical features. First, the aspect-ratio limitations are considered by comparing two inherently different techniques. The stable inspection of reference features is important, while trying to maximize the spatial extent of the measured features. Second, the measurement method is analyzed in two ways: by using a limited sample of the features to increase stability and eliminate interference from neighboring features; by varying the number of scan tracks, which greatly affects the measurement time.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Maraging steel is an iron-nickel steel alloy which achieves its superior strength, hardness and toughness by aging the martensite phase.In earlier investigations, however, the toughness of selective laser melted (SLM) and subsequent aged maraging steel was found to be low.Several authors attribute this to the large oxides present in the finished product.In this work, the origin for these oxides is investigated by using microscopy and spectroscopy.The analysis is done on specimens produced under different processing conditions and the most important characteristics of the inclusions are discussed.It is found that during the SLM process, an oxide layer containing Al and Ti is created on top of each layer.Upon melting the next layer, the oxide layer is broken and dragged further.Therefore, accumulations of oxide material are found in the final product as large, irregularly shaped inclusions.